Modalities for simultaneous therapy and diagnostics, known as theranostics, have gained significant interest for real-time biomedical imaging and site-specific treatment of the various diseases and conditions, including cancer. Phototherapy is a widely accepted non-invasive clinical approach to eradicate cancer, due in part, to the minimal side effects resulting from the selective illumination of the cancer site with light of an appropriate wavelength, while leaving healthy tissue untouched. When represented by photodynamic (PDT) and photothermal (PTT) therapies, the phototherapy requires light and a photosensitizer to generate reactive oxygen species and heat, respectively. The general procedure for PDT typically involves administration of non-toxic photoactive drugs (photosensitizers) which, upon exposure to light of specific wavelengths, damage cancer cells by producing reactive oxygen species (ROS). Unlike PDT, PTT does not require oxygen accessibility to damage targeted tissues, and by generating localized hyperthermia from absorbed light, PTT can be used to treat tissue that has a low oxygen concentration, such as low vascularized tumors.
For clinically relevant use, optical agents with absorption/emission in the near-infrared (NIR) window (about 650-900 nm) are advantageous because of the greater light penetration due to lower absorption and scatter from biological components. Therefore, there has been increased interest in the development and application of theranostic agents that can be activated by light with a wavelength in the NIR optical window. Body tissue is comparatively transparent in this spectral window, and so NIR light can be used for activation of photosensitizers accumulated in deep-seated cancer tumors without causing phototoxicity to normal, healthy tissue. Moreover, fluorescence imaging in the NIR optical window holds much promise due to minimal tissue autofluorescence and light scattering.
Due to their pronounced photophysical properties in the NIR range, the successful application of NIR dyes was reported in biomedical field, including for fluorescent imaging and phototherapy. Despite this interest, indocyanine green (ICG) is currently the only NIR dye FDA-approved as a clinical imaging agent. ICG has also been studied for PDT and PTT applications. However, low photostability in aqueous media resulting in a fast photodegradation, and quick clearance from the body significantly hampered the clinical application of ICG with respect to PDT and PTT, and thus hampered the possibility of ICG becoming a single theranostic agent in vivo.